Acid-base status in liver cirrhosis. Disturbances in stable, terminal and portal-caval shunted patients.

Acid-base status was determined in 86 patients with cirrhosis of the liver. Group I comprised 55 patients living more than 3 months after examination (stable). Another 18 stable patients with a surgical porta-caval shunt (p.c.a.) formed group II. Group III consisted of 12 terminal patients without p.c.a. examined within the last week of life. With respect to liver function group II was intermediate between I and III. The most common acid-base disturbance in group I was compensated respiratory alkalosis (20%) followed by compensated metabolic alkalosis (15%). 50% of group II presented compensated respiratory alkalosis. 85% of group III showed metabolic acidosis, which was compensated in only half of the patients. Respiratory alkalosis seemed more related to impairment of liver function than to portasystemic shunting. The genesis of the terminal metabolic acidosis was complex. Renal function was reduced in 92% of group III, and lactic acidosis was found in 36%. In this group hepatic function was most severely impaired, and 60% were hypotensive. These disturbances were not related to aetiology or treatment of the liver disease.     

慢性肝衰竭和失代偿期肝硬化患者血气分析的变化

目的探讨慢性肝衰竭和失代偿期肝硬化患者血气分析变化的临床意义。方法回顾性分析我科收治的37例慢性肝衰竭和失代偿期肝硬化患者的血气分析资料。结果2例患者出现明显的缺氧表现,4例患者出现立位性缺氧表现,11例患者感轻度胸闷;在36例存在酸碱失衡的患者,慢性肝衰竭组存在单纯酸碱失衡9例,两重酸碱失衡10例,三重酸碱失衡2例,失代偿期肝硬化组存在单纯酸碱失衡8例,两重酸碱失衡7例。两组患者在酸碱失衡的类型方面无统计学差异;两组均以碱中毒为主。慢性肝衰竭组中比例较高的三种类型依次为呼吸性碱中毒合并代谢性酸中毒（38．1％）、呼吸性碱中毒（23．8％）和代谢性碱中毒（14．3％）,单纯性代谢性酸中毒比例最低（4．8％）。失代偿期肝硬化组中比例较高的三种类型依次为呼吸陛碱中毒（46．7％）、呼吸性碱中毒合并代谢性碱中毒（26．7％）和呼吸性碱中毒合并代谢性酸中毒（20．0％）,代谢性碱中毒比例最低（6．7％）。结论慢性肝衰竭和失代偿期肝硬化患者存在酸碱失衡和低氧血症,动态监测血气分析并及时对症治疗对此类患眷具有重要的临床意义。     

Metabolic acidosis in the alcoholic: A pathophysiologic approach

The purpose of this paper is to review the acid-base abnormalities in patients presenting with metabolic acidosis due to acute ethanol ingestion and to review the theoretical constraints on ethanol metabolism in the liver. Alcohol-induced acidosis is a mixed acid-base disturbance. Metabolic acidosis is due to lactic acidosis, ketoacidosis and acetic acidosis but the degree of each varies from patient to patient. Metabolic alkalosis is frequently present due to ethanol-induced vomiting. However, it could be overlooked because of an indirect loss of sodium bicarbonate (as sodium B-hydroxybutyrate in the urine). Nevertheless, the accompanying reduction in ECF volume may play an important role in the pathogenesis of alcoholic acidosis because it could lead to a relative insulin deficiency. Treatment of alcohol acidosis should include sodium, chloride, potassium, phosphorus, magnesium and thiamine replacements slong with attention to concomitant clinical problems. Unless hypoglycemia is present, glucose need not be given immediately. We feel that insulin should be withheld unless life-threatening acidemia is present or expected. Lastly, alcohol need not be detected on admission to make the diagnosis of this metabolic disturbance. However, when present, it could contribute directly to the lactic, acetic and B-hydroxybutyric acidoses. With respect to the theoretical constraints on ethanol metabolism, it appears that “overproduction” of NADH in the liver is best averted by converting ethanol to B-hydroxybutyric acid.     

Equilibrium of acidifying and alkalinizing metabolic acid-base disorders in cirrhosis.

BACKGROUND AND AIMS: Conflicting results exist with regard to metabolic acid-base status in liver cirrhosis, when the classic concept of acid-base analysis is applied. The influence of the common disturbances of water, electrolytes and albumin on acid-base status in cirrhosis has not been studied. The aim of this study was to clarify acid-base status in cirrhotic patients by analyzing all parameters with possible impact on acid-base equilibrium. PATIENTS AND METHODS: Fifty stable cirrhotic patients admitted to a university hospital. Arterial acid-base status was analyzed using the principles of physical chemistry and compared with 10 healthy controls. RESULTS: Apart from mild hypoalbuminemic alkalosis, acid-base state was normal in Child-Pugh A cirrhosis. Respiratory alkalosis was the net acid-base disorder in Child-Pugh B and C cirrhosis with a normal overall metabolic acid-base state (Base excess-1.0 (-3.6 to 1.6) vs 1.1 (-0.2 to 1.1) mmol/l, P = 0.136, compared with healthy controls, median (interquartile range)). Absence of an apparent metabolic acid-base disorder was based on an equilibrium of hypoalbuminemic alkalosis and of dilutional acidosis and hyperchloremic acidosis. CONCLUSION: A balance of offsetting acidifying and alkalinizing metabolic acid-base disorders leaves the net metabolic acid-base status unchanged in cirrhosis.     

Metabolic alkalosis in diabetic ketosis: a case report

A mixed metabolic alkalosis and metabolic acidosis, resulting in an alkalemic state, occurred in a hyperlipemic patient with previously diagnosed non insulin dependent diabetes. The metabolic alkalosis, due to large loss of gastric HCl, was more severe than the diabetic acidosis and resulted in an alkaline blood pH. Initially the metabolic acidosis was due to ketoacidosis and coexistent lactic acidosis. During the improvement of the alkalemic and hyperglycemic state, lactic acidosis disappeared but a paradoxical rise of plasma NEFA and ketone body concentrations supervened so that the high anion gap metabolic acidosis was virtually unchanged. The rise of plasma NEFA was probably related to the marked removal of plasma triglycerides, by insulin activation of lipoprotein lipase, and consequent saturation of the pathways of fatty acid incorporation into adipose tissue.     

Arzneimittelassoziierte St?rungen des S?ure-Basen-Haushalts

Renal elimination of drugs and/or their metabolites may interact with different parts of the renal tubule system resulting in drug-induced acid-base disorders. Drug withdrawal or dose adjustment is the consequence. Antibiotic-related changes include many different acid-base disorders. Penicillin might cause hypokalemia, metabolic alkalosis or high-anion metabolic acidosis, aminoglycosides and tetracyclines are associated with Fanconi syndrome. Gentamicin may cause hypokalemic metabolic alkalosis together with hypomagnesemia and hypokalemia. Treatment with loop diuretics might result in hypochloremic metabolic acidosis nowadays termed chloride-depletion alkalosis for pathophysiological reasons. Using potassium-sparing diuretics, a mild hyperchloremic metabolic acidosis along with hyperkalemia has been reported. The incidence of calcium-alkali syndrome classified by the trias hypercalcemia, metabolic alkalosis and renal failure with polyuria is increasing due to the widespread use of vitamin D and calcium supplementation. Severe metabolic acidosis is associated with propofol use (propofol-related syndrome) as well as drug use containing propylene glycol (e.g. diazepam).     

肝硬变腹水患者钾钠氯及酸碱失衡

目的研究肝硬变腹水患者的钾、钠、氯及酸碱失衡。方法肝硬变腹水患者１５４例，血Ｋ＋、Ｎａ＋、Ｃｌ－测定采用ＥＥＬ公司自动分析仪及火焰光度计。血气及酸碱度测定采用ＩＬ１３０２型自动微机分析仪。结果低血钾者５７例，高血钾者６例，低血钠者８１例，高血钠者１２例，低血氯者３４例，高血氯者８例。２４例血气及酸碱度测定结果显示，以碱中毒者为主。依次为呼碱、呼碱＋代酸、代酸、代碱、呼酸。本组高血钾、低血钠与Ｃｈｉｌｄ分级、ＢＵＮ、Ｃｒ值相关。从本组资料表明，重症肝硬变腹水患者水盐代谢失衡多为医源性所致，且加重原有失衡。高钾血症、急性低钠血症及高钠血症大多如此，多为住院后发生，常可危及生命。结论肝硬变腹水患者的高钾血症、低钠血症和高钠血症大多在肝肾功能低下，不适当的治疗所致，是影响预后的重要因素     

Electrolyte and Acid–Base Disturbances in End-Stage Liver Disease: A Physiopathological Approach

Electrolyte and acid–base disturbances are frequent in patients with end-stage liver disease; the underlying physiopathological mechanisms are often complex and represent a diagnostic and therapeutic challenge to the physician. Usually, these disorders do not develop in compensated cirrhotic patients, but with the onset of the classic complications of cirrhosis such as ascites, renal failure, spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte, and acid–base disturbances emerge. Hyponatremia parallels ascites formation and is a well-known trigger of hepatic encephalopathy; its management in this particular population poses a risky challenge due to the high susceptibility of cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease and resulting from its management make these patients particularly susceptible to potassium depletion even in the setting of normokalemia. Acid–base disturbances range from classical respiratory alkalosis to high anion gap metabolic acidosis, almost comprising the full acid–base spectrum. Because most electrolyte and acid–base disturbances are managed in terms of their underlying trigger factors, a systematic physiopathological approach to their diagnosis and treatment is required.     

Acid-base disturbances in gastrointestinal disease

Gastrointestinal disorders are associated with severe and often complex acid-base disturbances. We review the most important types of metabolic alkalosis and metabolic acidosis associated with gastrointestinal disorders, excluding liver disease. Special emphasis is placed on pathophysiologic mechanisms. This information may help the clinician understand the generation and maintenance of these disorders and to plan an effective therapeutic approach.     

Acid-base disturbances in critically ill patients with cirrhosis.

BACKGROUND/AIMS: The equilibrium of offsetting metabolic acid-base disorders in stable cirrhosis might be lost during episodes of hepatic decompensation, haemorrhage or sepsis. The purpose of this study was to determine whether the acid-base state is destabilized in critically ill patients with cirrhosis and whether this is associated with mortality. PATIENTS AND METHOD: One-hundred and eighty-one consecutive patients with cirrhosis were investigated in a prospective observational cohort study on admission to a medical intensive care unit (ICU) of a university hospital. Arterial acid-base state was assessed according to the Gilfix methodology. Clinical data, ICU mortality and hospital mortality were recorded. MAIN RESULTS: Patients had net metabolic acidosis owing to unmeasured anions and owing to hyperchloraemic, dilutional and lactic acidosis. Lactic acidosis, acidemia and acute renal failure on ICU admission were associated with increased mortality. Lactate and pH discriminated survivors from non-survivors. The presence of lactic acidosis could not always be recognized by customary acid-base parameters. CONCLUSION: The stable equilibrium of acid-base disorders is lost when patients with cirrhosis become critically ill. Lactic acidosis and acidaemia are associated with increased ICU mortality caused by severe underlying organ dysfunction.     

Severe lactic acidosis following theophylline overdose.

The patient with theophylline overdose commonly presents with gastrointestinal, cardiovascular, neurologic, and electrolyte abnormalities. Respiratory alkalosis is the most common acid-base alteration, but mild metabolic acidosis has been reported. Two cases of severe lactic acidosis (pH 6.67 and 6.63) in patients without hypoxemia, shock, or prolonged seizure activity are reported. Possible causative mechanisms and aspects of therapy are discussed. Theophylline toxicity should be considered when an unconscious patient with concurrent severe metabolic acidosis presents to the emergency department.     

Distinctive acid-base pattern in Wernicke's encephalopathy

Wernicke's encephalopathy may result in severe morbidity and possible mortality when unrecognized. We report a distinctive acid-base pattern that has not been associated with this syndrome. This is a case series of patients with Wernicke's encephalopathy who had an arterial blood gas measurement performed on initial presentation. Exclusion criteria were patients with an unclear diagnosis of Wernicke's encephalopathy and those for whom no arterial blood gas measurement was performed. Four patients with Wernicke's encephalopathy were included in the analysis. All 4 patients exhibited an anion-gap (primary) metabolic acidosis, accompanied by a primary respiratory alkalosis. Three of 4 patients exhibited a significant lactic acidosis. None of the patients had any competing diagnoses or dysfunction to account for this acid-base pattern. Patients with Wernicke's encephalopathy may exhibit a distinctive acid-base pattern consisting of a primary metabolic acidosis in conjunction with a primary respiratory alkalosis. Observation of this acid-base disturbance should prompt clinicians to consider thiamine deficiency disorders as a possible cause.     

Organic acids in urine of patients with congenital lactic acidoses: An aid to differential diagnosis

The differential diagnosis of patients with apparent congenital lactic acidoses poses one of the most intractable problems in the study of patients with disorders of organic acid metabolism. An outline of the factors leading to a lactic acidosis, particularly in infants and young children, together with a brief review of the known causes of congenital lactic acidosis, are presented. Quantitative examination of the organic acids excreted by patients with proven enzyme deficiencies causing congenital lactic acidosis has demonstrated the characteristic patterns that are associated with specific disorders of this kind. After exclusion of uninherited, acquired and secondary metabolic causes of lactic acidosis, these quantitative patterns of organic acid excretion, together with other clinical and biochemical observations, provide valuable indicators of the area of the underlying primary metabolic disorder for subsequent selected, confirmatory, enzymology. The study of organic acids has a key and central role in the approach to the clinical and biochemical investigation and diagnosis of patients with congenital lactic acidoses.     

Acid-base disturbances in acute asthma

The clinical features, arterial blood gases, and acid-base profile were examined in 229 consecutive episodes of acute asthma in 170 patients who required hospitalization. A simple respiratory alkalosis was the most common acid-base disturbance, occurring in 48 percent of the episodes. Metabolic acidosis, either alone or as part of a mixed disturbance, was noted in 28 percent. Of 60 episodes presenting with respiratory acidosis, 37 (62 percent) had a coexistent metabolic acidosis. Metabolic acidosis was more likely to occur in male subjects and in patients with evidence of more severe airflow obstruction. Patients with metabolic acidosis had an average anion gap of 15.8 mEq/L; these patients were more hypoxemic than those without metabolic acidosis and there was a significant inverse correlation between the anion gap and the degree of hypoxemia. We conclude that metabolic acidosis is a common finding in acute, severe asthma and suggest that the pathogenesis of lactic acidosis is multifactorial and includes contributions from lactate production by respiratory muscles, tissue hypoxia, and intracellular alkalosis.     

Acid-base disturbances in liver disease

There are several important associations between the liver and acid-base balance. First, primarily because of its metabolism of certain cationic amino acids and organic acid anions, particularly lactate, the liver has a surprisingly important influence on normal acid-base homeostasis. Second, in the presence of the necessary pathogenic milieu, the liver may produce a life-threatening number of hydrogen ions. Examples include accelerated ketogenesis during insulinopenic states, or lactate production during severe hepatic parenchymal hypoxia. Third, patients with various types of liver disease, both acute and chronic, often develop complicating acid-base disturbances. In addition, liver disease may predispose the patient to a particular acid-base disorder such as phenformin-induced lactic acidosis. Finally, the acid-base disturbance may be a complication of therapy, as when diuretic therapy directed at ascites results in metabolic alkalosis.     

Hyponatremia in patients with ascites complicating liver cirrhosis]

Eighty unselected cases of hyponatremia complicating liver cirrhosis were analysed. Of these cases, 20 had sodium levels less than 135 mmol/L, 48 less than or equal to 130 mmol/L and 12 less than or equal to 125 mmol/L. 5 cases developed acute hyponatremic syndrome after abdominal paracentesis and high-dose of diuretics. Of these 5 cases, 1 died and 4 recovered after immediate infusion of 3% sodium chloride (200-300 ml/d intravenously for 7-10 days). Both the crystal and colloid pressure of blood determined in 10 cases were less than normal. The sodium level of the ascitic fluid determined in 5 cases was higher than that of serum. Respiratory alkalosis complicated with metabolic alkalosis or acidosis were the main features of acid-base disorders. These might be due to alkalinizing agents therapy, infection and hepato-renal syndrome. Based on these clinical studies, it was shown that paracentesis and diuretics are the main causes of acute hyponatremic syndrome, so these measures should be taken carefully in patients with hyponatremic state previously, especially in patients with poor general, hepatic and renal conditions.     

Acid-base disorders in hyperglycemia of insulin-dependent diabetic patients on chronic dialysis

The authors studied hyperglycemia occurring in insulin-dependent diabetic patients on chronic dialysis to determine the types of associated acid-base disorders, their treatment, and any differences from hyperglycemia in diabetic patients with intact renal function. Eighty-eight episodes of serum glucose greater than 25 mmol/L were observed, 23 in hemodialysis patients and 65 in patients on continuous peritoneal dialysis. Treatment consisted of low-dose insulin in 77 episodes and low-dose insulin plus saline in 11; no base was administered. Seventeen episodes (19%) presented with ketoacidosis. Arterial blood gas determinations were carried out at presentation in 37 of the episodes without ketoacidosis. Of these, 12 had respiratory alkalosis, six had respiratory acidosis and severe pulmonary edema, 14 had other single or mixed acid-base disorders, and only five had normal acid-base status. Insulin corrected the ketoacidosis in all instances and both pulmonary edema and respiratory acidosis in five of six instances. In eight cases metabolic alkalosis developed during treatment, without external acid loss. At the completion of treatment respiratory alkalosis was present in half the cases. No difference was noted between patients treated with hemodialysis or peritoneal dialysis. Insulin alone is sufficient for the management of hyperglycemia in dialysis patients. Certain acid-base disorders persist, but do not need further treatment. Hyperglycemia in patients on dialysis is characterized by infrequent development of metabolic acidosis and frequent presentation with respiratory alkalosis, by respiratory acidosis that is corrected by insulin, and by metabolic alkalosis developing during treatment without external cause.     

Disorders of fructose metabolism.

There are fundamental differences between the metabolic fate of fructose and of glucose. Whereas the metabolism of glucose is controlled by hormones such as insulin, fructose uptake and phosphorylation in the liver occurs independently of hormones and its ultimate metabolic fate is unpredictable. Essential fructosuria, a harmless inherited anomaly of fructose metabolism, is the least harmful of the disorders of fructose metabolism. Hereditary fructose intolerance and fructose-1,6-diphosphatase deficiency are discussed in greater detail with regard to biochemical abnormalities and clinical aspects. HFI is most serious in bottle-fed infants who cannot reject their sucrose-containing diet. Patients with HFI will have no clinical symptoms if kept on a fructose-free diet. In contrast, patients with fructose-1,6-diphosphatase deficiency can tolerate frucose. However, severe infections precipitate attacks of hypoglycaemia and lactic acidosis.     

Lactic acidosis associated with cirrhosis, hepatoma, hemoperitoneum, and hyperphosphatemia

A patient with cirrhosis developed hemoperitoneum, lactic acidosis, and hyperphosphatemia in the absence of shock. At post-mortem examination occult multicentric hepatocellular carcinoma eroding the liver capsule was present. The case emphasizes the central role of the liver in lactic acidosis, indicates that hemoperitoneum may precipitate this complication, and documents the association of lactic acidosis and hyperphosphatemia.     

The treatment of diabetes mellitus of patients with chronic liver disease

About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.